Fixed Dose Combination of Dapagliflozin, Glimepiride and Extended-release Metformin Tablets in Patients with Type 2 Diabetes Poorly Controlled by Metformin and Glimepiride: A Phase III, Open Label, Randomized Clinical Study in India

Overview

Journal Diabetes Obes Metab

Specialty Endocrinology

Date 2025 Feb 14

PMID 39950245

Authors

Rakesh Sahay

Dinesh Gangwani

Manish Singh

Sandeep Gupta

Narendra Kale

Manoj Srivastava

Prakash Kurmi

Jayesh Ambaliya

Nilesh Lomte

Sandip Gofne

Saurabh Agarwal

Priyanka Kashid

Vikas Agarwal

Pradeep Rai

Surendra Sharma

L Sreenivasa Murthy

Mandodari Rajurkar

Shruti Saha

Piyush Patel

Dipak Patil

Pravin Ghadge

Lalit Lakhwani

Suyog Mehta

Sadhna J Joglekar

Affiliations

Soon will be listed here.

Abstract

Aim: To evaluate the efficacy and safety of a triple fixed-dose combination (FDC) therapy of dapagliflozin + glimepiride + metformin hydrochloride extended-release (DAPA + GLIM + MET ER) tablets in Indian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by combination of GLIM + MET.

Materials And Methods: A phase III, randomized, open-label, active-controlled study was conducted for a maximum 30 weeks (primary treatment [16 weeks]; uptitration [12 weeks] and follow-up [2 weeks]). Eligible patients were randomized in a 1:1 ratio to receive either the FDC of DAPA + GLIM + MET ER or the FDC of GLIM + MET prolonged-release (PR) once-daily. The primary efficacy endpoint was a change in glycated haemoglobin (HbA1c) from baseline to week 16.

Results: The mean reduction in HbA1c from baseline to week 16 was significantly greater with the FDC of DAPA + GLIM + MET ER compared to the FDC of GLIM + MET PR (-1.98% ± 1.01% vs. -1.64% ± 0.86%, p = 0.0047). The mean reduction in HbA1c from baseline to week 12 was significantly greater with the FDC of DAPA + GLIM + MET ER versus dual FDC (p < 0.0001). The proportion of patients achieving HbA1c <7.0% was significantly greater with the FDC of DAPA + GLIM + MET ER versus dual FDC at week 12 (19.1% vs. 6.5%; p = 0.0002) and week 16 (52.6% vs. 36.7%; p = 0.0015). A significant decrease in HbA1c, fasting and post-prandial blood glucose from baseline to weeks 12, 16, and 28 was observed in both arms. The incidence of TEAEs was similar across both arms.

Conclusion: This study demonstrated that the FDC of DAPA + GLIM + MET ER tablets once daily was significantly better than dual FDC in achieving glycaemic control in patients with poorly controlled T2DM. Both treatments were well-tolerated.

Trial Registration: CTRI/2022/03/041424, registered on 28 March 2022.

Citing Articles

Fixed dose combination of dapagliflozin, glimepiride and extended-release metformin tablets in patients with type 2 diabetes poorly controlled by metformin and glimepiride: A phase III, open label, randomized clinical study in India.

Sahay R, Gangwani D, Singh M, Gupta S, Kale N, Srivastava M Diabetes Obes Metab. 2025; 27(4):2193-2205.

PMID: 39950245 PMC: 11885079. DOI: 10.1111/dom.16218.

References

. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care. 2023; 47(Suppl 1):S158-S178. PMC: 10725810. DOI: 10.2337/dc24-S009. View

Garber A, Abrahamson M, Barzilay J, Blonde L, Bloomgarden Z, Bush M . CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY. Endocr Pract. 2016; 22(1):84-113. DOI: 10.4158/EP151126.CS. View

Raghavan S, Vassy J, Ho Y, Song R, Gagnon D, Cho K . Diabetes Mellitus-Related All-Cause and Cardiovascular Mortality in a National Cohort of Adults. J Am Heart Assoc. 2019; 8(4):e011295. PMC: 6405678. DOI: 10.1161/JAHA.118.011295. View

Korytkowski M . Sulfonylurea treatment of type 2 diabetes mellitus: focus on glimepiride. Pharmacotherapy. 2004; 24(5):606-20. DOI: 10.1592/phco.24.6.606.34752. View

Sahay R, Gangwani D, Singh M, Gupta S, Kale N, Srivastava M . Fixed dose combination of dapagliflozin, glimepiride and extended-release metformin tablets in patients with type 2 diabetes poorly controlled by metformin and glimepiride: A phase III, open label, randomized clinical study in India. Diabetes Obes Metab. 2025; 27(4):2193-2205. PMC: 11885079. DOI: 10.1111/dom.16218. View

Kalra S . Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their Basic and Clinical Pharmacology. Diabetes Ther. 2014; 5(2):355-66. PMC: 4269649. DOI: 10.1007/s13300-014-0089-4. View

. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013; 310(20):2191-4. DOI: 10.1001/jama.2013.281053. View

Arya D, Chowdhury S, Chawla R, Das A, Ganie M, Prasanna Kumar K . Clinical Benefits of Fixed Dose Combinations Translated to Improved Patient Compliance. J Assoc Physicians India. 2019; 67(12):58-64. View

Min S, Yoon J, Moon S, Hahn S, Cho Y . Combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor in type 2 diabetes: a systematic review with meta-analysis. Sci Rep. 2018; 8(1):4466. PMC: 5849757. DOI: 10.1038/s41598-018-22658-2. View

10.

Anand S, Shivashankar R, Ali M, Kondal D, Binukumar B, Montez-Rath M . Prevalence of chronic kidney disease in two major Indian cities and projections for associated cardiovascular disease. Kidney Int. 2015; 88(1):178-85. PMC: 4490055. DOI: 10.1038/ki.2015.58. View

11.

Rozenfeld Y, Hunt J, Plauschinat C, Wong K . Oral antidiabetic medication adherence and glycemic control in managed care. Am J Manag Care. 2008; 14(2):71-5. View

12.

Rosenstock J, Kahn S, Johansen O, Zinman B, Espeland M, Woerle H . Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA. 2019; 322(12):1155-1166. PMC: 6763993. DOI: 10.1001/jama.2019.13772. View

13.

Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S . Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015; 38(3):365-72. DOI: 10.2337/dc14-0666. View

14.

Ji L, Han P, Liu Y, Yang G, Dieu Van N, Vijapurkar U . Canagliflozin in Asian patients with type 2 diabetes on metformin alone or metformin in combination with sulphonylurea. Diabetes Obes Metab. 2014; 17(1):23-31. DOI: 10.1111/dom.12385. View

15.

Wiviott S, Raz I, Bonaca M, Mosenzon O, Kato E, Cahn A . Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2018; 380(4):347-357. DOI: 10.1056/NEJMoa1812389. View

16.

Einarson T, Acs A, Ludwig C, Panton U . Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018; 17(1):83. PMC: 5994068. DOI: 10.1186/s12933-018-0728-6. View

17.

Inzucchi S . Is It Time to Change the Type 2 Diabetes Treatment Paradigm? No! Metformin Should Remain the Foundation Therapy for Type 2 Diabetes. Diabetes Care. 2017; 40(8):1128-1132. DOI: 10.2337/dc16-2372. View

18.

Inzucchi S, Bergenstal R, Buse J, Diamant M, Ferrannini E, Nauck M . Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012; 35(6):1364-79. PMC: 3357214. DOI: 10.2337/dc12-0413. View

19.

Chawla R, Madhu S, Makkar B, Ghosh S, Saboo B, Kalra S . RSSDI-ESI Clinical Practice Recommendations for the Management of Type 2 Diabetes Mellitus 2020. Indian J Endocrinol Metab. 2020; 24(1):1-122. PMC: 7328526. DOI: 10.4103/ijem.IJEM_225_20. View

20.

Stratton I, Adler A, Neil H, Matthews D, Manley S, Cull C . Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000; 321(7258):405-12. PMC: 27454. DOI: 10.1136/bmj.321.7258.405. View